Basal lipid kinetics and lipolytic response to B-adrenergic stimulation are altered in persons with severe or upper body obesity. We evaluated the effect of diet-induced weight loss on lipid metabolism in persons with severe upper-body obesity in two study protocols. In protocol 1, palmitate and glycerol rates of appearance (Ra) in plasma were determined during basal conditions and during a 1-h epinephrine infusion (n=7, BMI = 41.3.2kg/m2) before and after a 20.4+3.0 kg weight loss. Basal total glycerol and palmitate Ra decreased from 231.0+19.4 and 166.2+16.6 umol.min-1, respectively, before weight loss to 162.7+9.5 and 105.0+9.7 umol.min-1, respectively, after weight loss (p< 0.01). However, glycerol and palmitate Ra expressed per kg fat mass were similar both before and after weight loss. The total increase in glycerol and palmitate Ra during epinephrine infusion was greater after (541+36 and 255+26 umol.kg fat mass -1) than before (355+29 and 117+27 umol.kg fat mass -1) weight loss (p<0.05). In protocol 2, subcutaneous abdominal adipose tissue was obtained before and after a 14.4+2.1 kg weight loss (n=5, BMI = 41.6+2.6kg/m2). Weight loss caused a 38+8% decrease in adipocyte hormone-sensitive lipase concentration (p<0.05) but was not associated with any consistent changes in the concentrations of Gi1a, Gi2a, and Gsa. We conclude that diet-induced weight loss ameliorates the increase in basal lipolytic rates and the decreased lipolytic response to betaadrenergic stimulation in persons with severe upper-body obesity. These alterations are associated with changes in cellular hormone sensitive lipase but not G-protein concentrations.